Abstract and Introduction
Abstract
A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.
Introduction
Plaque-type psoriasis is a chronic inflammatory skin disease characterized by thickened red plaques and silvery lamellar scales predominantly on the scalp, trunk and extensor surfaces.[1] The prevalence is about 2–3% in Western countries.[2,3] An increased understanding of the immune mechanisms underlying plaque formation has driven recent advances in psoriasis treatment.[4–6] However, an intriguing characteristic of psoriasis is the tendency of lesions to recur in the same anatomical locations after therapy is discontinued following plaque resolution.
Available evidence supports the concept of a local immunological 'memory' in resolved sites after disappearance of visible inflammation.[7] This review provides a historical narrative of the immunopathology of psoriasis lesion recurrence, including insights from emerging data on the molecular and cellular basis of disease memory in resolved psoriatic plaques.
The British Journal of Dermatology. 2022;186(5):773-781. © 2022 Blackwell Publishing
